Cardiac surgery, especially that involving cardioplegia (CP) and cardiopulmonary bypass (CPB), is associated with significant changes in vasomotor regulation and subsequent organ injury such as neurocognitive deficit, stroke, renal and mesenteric failure, post-operative systemic hypotension and coronary spasm. Diabetes is also associated with severe autonomic dysfunction and vasomotor regulation, as well as with increased morbidity and mortality after surgical procedures. The goal of the proposed research is to determine the effect of well-controlled and poorly controlled diabetes mellitus on alteration in vascular signal transduction and function and to investigate the changes that occur in these patients undergoing heart surgery with CP and CPB. Specifically, diabetes-dependent differences in post-surgical vascular function will be investigated with specific focus on 1) myogenic tone, 2) ?-drenergic and vasopressin signaling and contraction, 3) effects of glucose blood levels and their relationships with vascular function and clinical outcomes, in particular, neurocognitive function and 4) confounding effects of gender and age on diabetes-induced vascular alterations. This work will be accomplished through an exhaustive approach using molecular and cellular biology techniques to examine gene and protein expression and activation involved in maintaining vascular integrity and signaling following cardiac surgery. The results of these studies may have significant implications regarding the recovery of diabetic and other patients after cardiac surgery involving CP/CPB.